The renal nerves play a central role in the neurogenic control of body fluid homeostasis. The overall objective of this study is to investigate the role of afferent renal nerves in this process. Subtypes of renal afferent nerves are responsible to vascular, tubular, and hormonal factors in the kidney, but it is not known if these diverse stimuli exert specific reflex responses in efferent renal sympathetic activity. In addition, the afferent renal nerves belong to a group of nerves that release neuropeptides from their sensory endings. The principal neuropeptides reported in afferent renal nerves are substance P (SP), a natriuretic agent, and calcitonin gene related peptide (CGRP), a vasodilator. These are important modulators of local vascular resistance in many tissues but the functional significance of neuropeptide release in the kidney is not known. Pilot studies have demonstrated significant spillover of neuropeptide into the renal pelvis during activation of renal chemoreceptors and an inhibitory activity on vasoconstriction. The specific aims of these studies are: 1) to investigate the specificity of renorenal and renovisceral reflexes at the single efferent unit level and 2) to investigate the role of neuropeptides released from renal afferent nerves on renal vascular and tubular function. Methods: Aim 1 will involve electrophysiological recordings of sympathetic efferent activity in renal and genitofemoral nerves of anesthetized rats. Activity in individual efferent fibers will be measured and analyzed during a series of interventions designed to stimulate specific groups of renal afferent nerves and systemic arterial baroreceptors. Comparison of the responses of individual fibers to several stimuli will show the specificity of reflexes with respect to the target organ and the initiating afferent fibers. In Aim 2, SP and CGRP will be infused into the renal artery at physiological rates to investigate their action on renal excretory function by clearance techniques and on the renal vasculature from their ability to counteract the renal vasoconstrictor effects of angiotensin II and norepinephrine. The same techniques will be used to study the effects of endogenous SP and CGRP release during stimulation of afferent renal nerves. Selective antagonists will identify the effects of each neuropeptide on hemodynamic and excretory function. Neuropeptide release will be measured by radioimmunoassay and correlated with the activation of selected subtypes of renal afferent nerves. Significance: 1) These studies will provide new data on the specificity of renorenal reflex control of renal function at the single fiber level. 2) The importance of neuropeptide release from renal afferent nerves in the control of renal vascular and excretory function will be investigated for the first time.